Effects of chlorinated paraffins on rat liver microsomal activities and morphology

Short term effects of chlorinated paraffins with different length of the carbon chain and different degree of chlorination were investigated with respect to rat liver cytochrome P-450 mediated metabolism and liver cell morphology. When paraffins were administered by i.p. injection liver weights increased inversely with the length of the carbon chain. The short carbon chain paraffins with a high degree of chlorination increased the concentration of liver microsomal cytochrome P-450, inhibited the metabolism of 7-ethoxyresorufin but increased the metabolism of benzo(a)pyrene, especially the formation of the 4,5-diol metabolite. Short carbon chain paraffins gave rise to a proliferation of the smooth ER, increased the number of cytoplasmic fat droplets as well as the number and size of mitochondria and peroxisomes and finally induced the occurrence of autophagosomes and lysosomes. The fat droplets were preferentially degraded in lysosomes. In all respects the long carbon chain paraffins were less biologically active.     

Humorale Immunreaktionen an der hepatocellulären Plasmamembran bei der experimentellen chronisch aktiven Hepatitis im Kaninchen

Zusammenfassung Zur Induktion einer experimentellen chronisch aktiven Hepatitis (CAH) wurden Kaninchen mit humanem leberspezifischem Protein plus komplettem Freundschen Adjuvans langzeitimmunisiert. Nach 23wöchiger Versuchsdauer waren im Serum Antikörper gegen allogene hepatocelluläre Membranantigene mit Hilfe isolierter normaler Kaninchenhepatocyten bzw. in der passiven Hämagglutination mit leberspezifischem Membranprotein als Antigen nachweisbar. Gleichzeitig zeigten isolierte Hepatocyten dieser Tiere in vivo-fixiertes IgG an den Plasmamembranen in Form eines gemischt linear-granulären Fluoreszenzmusters. Mit der Raji-Zell-Technik wurden im Serum der Tiere Immunkomplexe gefunden. Eine chronisch aktive Hepatitis (CAH) hatte sich bei 3 von 16 Tieren entwickelt. Nach 44wöchiger Versuchsdauer bestand bei 10 von 15 Tieren und nach 78 Wochen bei 6 von 7 überlebenden Tieren eine CAH. Alle 7 überlebenden Tiere hatten im Serum Antikörper gegen Membranantigen isolierter Kaninchenhepatocyten und in vivo-fixiertes IgG an den hepatocellulären Plasmamembranen. Es wird angenommen, daß es sich um einen Autoantikörper gegen hepatocelluläres Membranantigen handelt. Darüber hinaus dürften in vivo an den Hepatocyten Immunkomplexe fixiert sein. Die pathogenetische Bedeutung dieser humoralen Immunphänomene ist ungeklärt.Die Autoren sind Mitglieder des Sonderforschungsbereiches 107     

Adult metachromatic leukodystrophy. I. Clinical manifestation in a female aged 44 years, previously diagnosed in the preclinical state.

In a 5-year follow-up of a case of adult metachromatic leukodystrophy, already diagnosed in the preclinical stage, the development of the symptoms of this disease could be studied in detail: initially, lack of drive, emotional lability and depressive mood. At the same time, pain in the arms and beginning gait disturbance. Later, impairment of memory and concentration, disorientation, inadequate behavior and progression of gait disturbance. Finally spastic atactic gait with small steps and dyspractic components, coordination disturbances with writing dysfunction, fast dysarthric speech, hyperkinetic activity, compulsory emotional outbursts and progressive dementia. Only minor neurological signs such as reflex abnormalities. In the EEG, slight slowing of frequencies compared to earlier tracings. Increasing diminution of nerve conduction velocity in the lower limbs. Only minor increase of CSF protein (51 mg%). In spite of normal vision, evoked visual potentials abnormal, response of optical and electrical blink reflexes delayed. Imperfect filling of gallbladder. No significant quantitative changes of the biochemical parameters compared with the findings made 5 years earlier (excretion of urinary sulfatides, diminished activity of arylfulfatase A in urine and leukocytes).     

Temperature dependence of the electrical and mechanical responses of the adductor pollicis muscle in humans

Changes at low temperatures of the electrical and mechanical activity of the adductor pollicis muscle were studied in 10 volunteers. Decreasing temperatures resulted in increased amplitude and duration of the negative phase and peak-to-peak amplitude of the evoked muscle action potential. Distal latency, electromechanical latency, contraction time, and half-relaxation time were also increased while isometric force, contraction velocity, and relaxation velocity were decreased. The increase of contraction time is greater over the temperature range below 28 degrees C than above 29 degrees C. Skin temperature differs significantly from muscle temperature, showing about 3 degrees C lower values during cooling and up to 4 degrees C higher values during rewarming with radiant heat.     

Clinical applications of EPR: overview and perspectives

The development and use of in vivo techniques for strictly experimental applications in animals has been very successful, and these results now have made possible some very attractive potential clinical applications. The area with the most obvious immediate, effective and widespread clinical use is oximetry, where EPR almost uniquely can make repeated and accurate measurements of pO2 in tissues. Such measurements can provide clinicians with information that can impact directly on diagnosis and therapy, especially for oncology, peripheral vascular disease and wound healing. The other area of immediate and timely importance is the unique ability of in vivo EPR to measure clinically significant exposures to ionizing radiation 'after-the-fact', such as may occur due to accidents, terrorism or nuclear war. There are a number of other capabilities of in vivo EPR that also potentially could become extensively used in human subjects. In pharmacology the unique capabilities of in vivo EPR to detect and characterize free radicals could be applied to measure free radical intermediates from drugs and oxidative process. A closely related area of potential widespread applications is the use of EPR to measure nitric oxide. These often unique capabilities, combined with the sensitivity of EPR spectra to the immediate environment (e.g. pH, molecular motion, charge) have already resulted in some very productive applications in animals and these are likely to expand substantially in the near future. They should provide a continually developing base for extending clinical uses of in vivo EPR. The challenges for achieving full implementation include adapting the spectrometer for safe and comfortable measurements in human subjects, achieving sufficient sensitivity for measurements at the sites of the pathophysiological processes that are being measured, and establishing a consensus on the clinical value of the measurements.     

Dynamic coupled metal transport-speciation model: application to assess a zinc-contaminated lake

A coupled metal transport and speciation/complexation model (TRANSPEC) has been developed to estimate the speciation and fate of multiple interconverting species in surface aquatic systems. Dynamic-TRANSPEC loosely, sequentially couples the speciation/complexation and fate modules that, for the unsteady state formulation, run alternatively at every time step. The speciation module first estimates species abundance using, in this version, MINEQL+ considering time-dependent changes in water and pore-water chemistry. The fate module is based on the quantitative water air sediment interaction (QWASI) model and fugacity/aquivalence formulation, with the option of using a pseudo-steady state solution to account for past discharges. Similarly to the QWASI model for organic contaminants, TRANSPEC assumes the instantaneous equilibrium distribution of metal species among dissolved, colloidal, and particulate phases based on ambient chemistry parameters that can be collected through conventional field methods. The model is illustrated with its application to Ross Lake (Manitoba, Canada) that has elevated Zn concentrations due to discharges over 70 years from a mining operation. Using measurements from field studies, the model reproduces year-round variations in Zn water concentrations. A 10-year projection for current conditions suggests decreasing Zn remobilization and export from the lake. Decreasing Zn loadings increases sediment-to-water transport but decreases water concentrations, and vice versa. Species distribution is affected by pH such that a decrease in pH increases metal export from the lake and vice versa.     

Phosphorylation of insulin-like growth factor binding protein-3 by deoxyribonucleic acid-dependent protein kinase reduces ligand binding and enhances nuclear accumulation

The IGF binding proteins (IGFBPs) regulate the mitogenic effects of IGFs in the extracellular environment. Several members of this family, including IGFBP-3, also appear to have IGF-independent effects on cell function. For IGFBP-3 and IGFBP-5, both of which are translocated to the cell nuclei, these effects may be related to their putative nuclear actions. Because reversible phosphorylation is an important mechanism for controlling nuclear protein import, we have examined the effect of phosphorylating IGFBP-3 with a number of serine/threonine protein kinases on its nuclear import. Phosphorylation of IGFBP-3 by the double-stranded DNA-dependent protein kinase (DNA-PK) increased both the nuclear import of IGFBP-3 and the binding of IGFBP-3 to components within the nucleus compared with nonphosphorylated IGFBP-3. However, there was no difference in the binding of the nuclear transport factor, importin beta, to nonphosphorylated and phosphorylated IGFBP-3. The ability of the DNA-PK phosphoform of IGFBP-3 to bind IGFs was severely attenuated, and in contrast to nonphosphorylated IGFBP-3, the DNA-PK phosphoform was unable to transport IGF-I to the nucleus. Furthermore, IGFBP-3 was phosphorylated by DNA-PK when complexed to IGF-I causing the phosphoform to release IGF-I. Together, these results suggest that when IGF-I is cotransported into the nucleus by IGFBP-3, phosphorylation of IGFBP-3 by nuclear DNA-PK provides a means for releasing bound IGF-I and creating a phosphoform of IGFBP-3 with increased affinity for nuclear components.     

Masseter reflex latencies and amplitudes are not influenced by supratentorial and cerebellar lesions

The aim of this study was to investigate possible influences of suprasegmental lesions on the masseter reflex. The masseter reflex was elicited in 54 patients with supratentorial (37 patients) or cerebellar (17 patients) lesions 3-11 days after the acute onset of clinical disease. Patients showing lesions within the pons and midbrain on thin-slice magnetic resonance imaging were excluded from evaluation. The testing procedure included an additional facilitating maneuver (opening and closing the jaw before tapping). Masseter reflex latencies, interside differences, and amplitudes were within the normal range in all patients. Latencies were not different with and without the facilitating maneuver. Amplitudes were significantly higher with the maneuver, but interside differences of amplitudes were unchanged. Masseter reflex abnormality can be taken as a reliable measure of direct involvement of the reflex arc.